The dopamine hypothesis of drug addiction and its potential therapeutic value.
The dopamine hypothesis of drug addiction and its potential therapeutic value.
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DOI：
10.3389/fpsyt.2011.00064
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发表时间：
2011
影响因子：
4.7
通讯作者：
Diana M
中科院分区：
文献类型：
--
作者：
Diana M
多巴胺（DA）的传递深受药物滥用的影响，DA功能的改变涉及药物成瘾的各个阶段，并可能在治疗上加以利用。特别是，基础研究已经证明，在酒精，阿片类药物，大麻素，和其他药物依赖性大鼠的DA神经元的电生理活动减少。此外，几乎所有药物依赖性啮齿动物的中脑核（Nacc）中的DA释放都减少。同时，这些研究得到了从酒精、尼古丁、阿片类药物和其他滥用药物戒断期间颅内自我刺激（ICSS）阈值增加的支持，从而表明ICSS的神经底物功能减退。因此，形态学评价馈入现实的计算分析的介质多刺神经元的Nacc，突触后对应的DA终端，显示了深刻的变化，在整个中脑边缘系统的结构和功能。与这些发现一致，人类成像研究显示，可卡因、海洛因和酒精依赖受试者的腹侧纹状体中多巴胺受体减少，伴随着内源性DA的释放减少，从而提供了“多巴胺贫乏”成瘾人脑的视觉证据。DA系统生理活性的持续降低导致了这样的想法，即其活性的增加，以恢复药物前水平，可能会产生显着的临床改善（减少渴望，复发和药物寻求/服用）。从理论上讲，它可以通过非手术和/或新的干预措施（如经颅磁刺激）来实现。它的解剖生理学原理作为一种可能的治疗援助酗酒者和其他成瘾者将被描述和提出作为一个理论框架，在人类成瘾者进行实验测试。
Dopamine (DA) transmission is deeply affected by drugs of abuse, and alterations in DA function are involved in the various phases of drug addiction and potentially exploitable therapeutically. In particular, basic studies have documented a reduction in the electrophysiological activity of DA neurons in alcohol, opiate, cannabinoid, and other drug-dependent rats. Further, DA release in the Nucleus accumbens (Nacc) is decreased in virtually all drug-dependent rodents. In parallel, these studies are supported by increments in intracranial self stimulation (ICSS) thresholds during withdrawal from alcohol, nicotine, opiates, and other drugs of abuse, thereby suggesting a hypofunction of the neural substrate of ICSS. Accordingly, morphological evaluations fed into realistic computational analysis of the medium spiny neuron of the Nacc, post-synaptic counterpart of DA terminals, show profound changes in structure and function of the entire mesolimbic system. In line with these findings, human imaging studies have shown a reduction of dopamine receptors accompanied by a lesser release of endogenous DA in the ventral striatum of cocaine, heroin, and alcohol-dependent subjects, thereby offering visual proof of the “dopamine-impoverished” addicted human brain. The lasting reduction in physiological activity of the DA system leads to the idea that an increment in its activity, to restore pre-drug levels, may yield significant clinical improvements (reduction of craving, relapse, and drug-seeking/taking). In theory, it may be achieved pharmacologically and/or with novel interventions such as transcranial magnetic stimulation (TMS). Its anatomo-physiological rationale as a possible therapeutic aid in alcoholics and other addicts will be described and proposed as a theoretical framework to be subjected to experimental testing in human addicts.